rs1927350

Positions:

• chr13-110466199-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.2038+137T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 988,302 control chromosomes in the GnomAD database, including 170,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27927 hom., cov: 33)
  • Exomes 𝑓: 0.57 (142404 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.997

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 13-110466199-T-G is Benign according to our data. Variant chr13-110466199-T-G is described in ClinVar as [Benign]. Clinvar id is 1273943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2038+137T>G		intron_variant		ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2038+137T>G		intron_variant		5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90568 AN: 152028 Hom.: 27894 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.574 AC: 479656 AN: 836156 Hom.: 142404 AF XY: 0.571 AC XY: 238722 AN XY: 417812

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.475

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.580

GnomAD4 genome AF: 0.596 AC: 90660 AN: 152146 Hom.: 27927 Cov.: 33 AF XY: 0.583 AC XY: 43368 AN XY: 74372

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.598

Alfa AF: 0.608 Hom.: 3526

Bravo AF: 0.606

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1927350; hg19: chr13-111118546; COSMIC: COSV64625577; COSMIC: COSV64625577;